Transcranial low-level laser (light) therapy: mechanisms and application to traumatic brain injury and beyond.

Low-level laser (or light) therapy (LLLT) is attracting growing interest to treat both stroke and traumatic brain injury (TBI). The fact that near-infrared (NIR) light can penetrate through the scalp and skull into the brain, allows non-invasive treatment to be carried out with a low likelihood of treatment-related adverse events. It is proposed that red and NIR light is absorbed by chromophores in the mitochondria of cells (which are particularly abundant in cortical neurons) leading to changes in gene transcription and upregulation of proteins involved in cell survival, antioxidant production, collagen synthesis, reduction of chronic inflammation and cell migration and proliferation. We developed two different models of TBI in mice: a closed head weight drop and an open skull controlled cortical impact (CCI). Transcranial laser therapy consisting of a single exposure 4 hours post-TBI to 36 J/cm(2) of various lasers was delivered to the closed head model. 810 nm or 660 nm laser significantly improved neurological severity score in TBI up to 4-weeks post-TBI. Laser therapy at 730 nm or 980 nm was ineffective. We then examined the effect of 0, 1, 3, and 14 daily 810 nm laser treatments in the CCI model. A single laser exposure gave a significant improvement while 3 laser exposures were better still. Our data suggest that transcranial LLLT is a promising treatment for acute (and chronic) TBI and may have much wider applications to neurodegenerative and psychiatric diseases. The lack of side-effects and paucity of alternative treatments for brain diseases should encourage more early clinical trials.